The Role of Sugar Alcohols in Caries Prevention

Although largely preventable, dental caries remains the most common chronic disease in children.¹ Caries prevention is challenging due to the disease’s multifactorial etiology and risk factors. The three primary factors attributed to the etiology of dental caries are the host (teeth), cariogenic microflora, and diet.^2,3 Specific to diet, early milestone research, such as the Vipeholm study,⁴ Hopewood House study,⁵ and Turku sugar studies,⁶ found a direct association between the consumption of dietary sugars and dental caries. Since then, voluminous research has been published on the role of dietary sugars in caries development.⁷ Without the presence of sugars, the chain of causation is incomplete and decay does not occur, demonstrating that dental caries is a diet-mediated disease.⁷

Upon ingestion of fermentable sugars such as sucrose, glucose, and fructose, acidogenic bacteria produce acid that can lower the pH of dental biofilm to levels that cause demineralization of teeth.⁸ Among the various dietary sugars, sucrose is thought to be the most cariogenic. Sucrose is readily fermented by cariogenic bacteria and serves as a substrate for synthesis of extracellular and intracellular polysaccharides that play roles in bacterial adhesion to enamel.⁹ The extracellular polysaccharides also may increase the porosity of the biofilm, thereby facilitating the diffusion of sugars to the microbiota in the deepest parts of the biofilm.¹⁰ High-sucrose biofilms also have notably lower concentrations of calcium, phosphate, and fluoride, thus limiting tooth remineralization.¹¹

Recently, the World Health Organization (WHO) recommended reducing the intake of “free sugars” while keeping sugar consumption to less than 10% of total energy intake.¹² Free sugars consist of added (monosaccharides and disaccharides) and naturally occurring sugars found in food products.

There has been ongoing interest in the use of sugar alcohols to replace traditional sugars in light of potential health benefits such as reduced cariogenicity and fewer calories, as well as de­creased glycemia and insulinaemia.¹³ This is because sugar alcohols are hydrogenated carbohydrates that are not readily metabolized by bacteria, making them less cariogenic when used as alternatives to dietary sugars, especially sucrose.¹⁴ The defining characteristic of sugar alcohols is the presence of an alcohol group in place of carbonyl group in the aldose and ketose moieties of mono-, di-, oligo-, and polysaccharides.¹³ Sugar alcohols also are referred to as polyol/polyhydric alcohol (eg, compounds containing three or more hydroxyl groups). Polyols can be acyclic compounds such xylitol, erythritol, and sorbitol, or cyclic polyols such as myo-inositol.¹⁵

As noted above, the noncariogenicity is common to all sugar alcohols because they are scarcely metabolized by microorganisms in the dental plaque.¹⁶ Thus, sugar alcohols can be classified as hypo- or nonacidogenic, with reduced or virtually no extracellular polysaccharide production.¹⁷ The fact that sugar alcohols do not produce extracellular polysaccharides is believed to be one of the reasons for their proven noncariogenicity. Another beneficial effect of sugar alcohol-based chewing gums is that chewing stimulates salivary secretion.¹⁸ Saliva can reduce caries due to its mechanical cleansing/flushing action, its ability to deliver ions for remineralization and buffer plaque acids, and via its own antibacterial properties.¹⁹

In 2010, Makinen¹⁵ suggested that the efficacy of sugar alcohols for caries prevention can be determined by each molecule’s number of hydroxyl groups, with erythritol ? xylitol > sorbitol. Yet the effect on caries rates between erythritol and xylitol is not fully established.¹⁵ In 1989, Grenby and Mistry²⁰ reported that the amount of polysaccharide matrices synthesized by incubated microorganisms varied between sugar alcohols, with sorbitol > mannitol > lactitol > xylitol.

Because sugar alcohols are poorly metabolized, they are only partially digested and ab­sorbed in the small intestine. As such, sugar alcohols may contribute to more frequent bowel movements, increased flatulence, and diarrhea. Tolerance to sugar alcohols may vary from person to person, but most adapt to polyols within a few days.²¹

Based on the evidence indicating that replacing sugars in the diet with sugar alcohols reduces the risk of dental caries, the United States Food and Drug Administration (FDA) approved a “do not promote dental caries” claim for various sugar alcohols such as xylitol, sorbitol, erythritol, mannitol, maltitol, hydrogenated starch hydrolysate (HSH), and lactilol.²² The FDA recently added isomalt to this list.²³ The purpose of this paper is to provide an evidence-based update on the commonly used sugar alcohols and their role in caries prevention.

XYLITOL

Xylitol (C₅H₁₂O₅) is a sugar alcohol that is a five-carbon sugar. It naturally occurs in many fruits and vegetables and is produced commercially from plants such as birch and other hard wood trees.²⁴ Xylitol is the most studied and thought to be most effective among sugar alcohols in reducing dental caries. However, there are conflicting results from research regarding the role of xylitol in caries prevention.

Twetman²⁵ reported that xylitol reduced dental caries when given in doses of at least 5 g three to four times per day. This article suggested that xylitol is nonfermentable, reduces the volume of dental plaque, prevents decreases in plaque pH, exerts a stimulating effect on saliva, and promotes selection of less virulent xylitol-resistant mutans streptococci (MS).²⁵

A systematic review was conducted in 2008 on the use of xylitol as part of an oral hygiene regimen to prevent caries. This review included two randomized clinical trials and four controlled clinical trials that compared xylitol chewing gum with no chewing gum. In their conclusions, authors noted that research gaps existed around the dose-response relationship and relative efficacy of different sugar alcohols.²⁶ Another systematic review by Antonio et al²⁷ concluded that xylitol-based candies and lozenges may help reduce the risk of noninterproximal caries but the level of evidence was noted as inconsistent and of limited quality.

Major health organizations have ex­pressed limited recommendations regarding the use of xylitol for the prevention of dental caries. A systematic review sponsored by the American Dental Association (ADA) Council on Scientific Affairs recommended that xylitol chewing gum marginally reduces the incidence of caries.²⁸ The 2014 US Preventive Services Task Force re­ported insufficient evidence to formally recommend xylitol’s routine use for caries prevention.²⁹ A Cochrane review found low-quality evidence to support the use of fluoride toothpaste containing xylitol over fluoride-only toothpaste for preventing dental caries in children’s permanent teeth, as well as insufficient evidence to support the role of other xylitol interventions in caries prevention.¹⁹ In addition, the American Academy of Pediatric Dentistry (AAPD) revised their policy on xylitol use in 2015 stating that the results from trials of xylitol aimed at reducing dental caries, transmission of MS from mothers to children, and reduction of MS levels in children varied and were inconclusive. The AAPD policy emphasized that most studies used very large doses and frequencies, which may be unrealistic in clinical practice.³⁰

In summary, the three possible ways in which xylitol may reduce caries are by substitution of cariogenic free sugars, saliva stimulation, and a possible antibacterial effect. The literature suggests that xylitol may be effective against S. mutans when given above the daily dose threshold of 5 g to 6 g per day in three or more divided doses. However, it is difficult to conclude if this anti-caries effect is over and above sugar substitution and saliva stimulation.¹⁹ Therefore, there is low-quality evidence that supports the inclusion of xylitol in a caries prevention regimen.

SORBITOL

The sugar alcohol sorbitol (C₆H₁₄O₆) is a bulk sweetener naturally found in some fruits and manufactured commercially from dextrose produced from cornstarch.^24,31 Though the mechanism of anti-cariogenic action is the same for sorbitol as for other sugar alcohols, Ikeda³² reported that MS can metabolize sorbitol and produce acid. The amount of acid produced, however, was far smaller than that produced from sucrose.

Van Loveren¹⁷ concluded that most clinical trials with sorbitol-sweetened gums have a caries preventive effect in comparison with no gum use. Due to the limited number of studies included in this review, however, the caries preventive effect was difficult to quantify.¹⁷ Deshpande and Jadad²⁶ concluded from a systematic review that sorbitol-alone chewing gum re­duced dental caries, but there is a re­search gap regarding the dose-response relationship. Conflicting evidence regarding the efficacy of sorbitol was reported by Splieth et al,³³ who found that the consumption of five xylitol lozenges per day for 4 weeks reduced acido­genicity of plaque. Such effects were not seen with sorbitol.

Makinen³⁴ reported in 2011 that dental plaque can become adapted to sorbitol and its efficacy may be weaker than xylitol. Mickenautsch and Yengopal³⁵ concluded from a systematic review that the evidence to support the use of xylitol over sorbitol is contradictory, with studies having high risk for bias and other confounders. They recommended that more high-quality randomized clinical trials be conducted to provide conclusive evidence regarding the efficacy of sorbitol.

ERYTHRITOL

Erythritol (C₄H₁₀O₄) is a natural tetritol sugar alcohol with four hydroxyl groups. It is a zero calorie sweetener and the newest sugar alcohol to be manufactured from cornstarch via a fermentation process. It occurs naturally in fruits, mushrooms, and fermentation-derived foods such as wine and cheese. Erythritol is rapidly absorbed in the small intestine, reducing the likelihood of laxative effects and increased flatulence.^24,31

In 2013, Runnel et al36 studied the effects of 3 years of erythritol candy consumption in school children. They found lower levels of acetic acid and propionic acid in dental plaque, as well as a reduction in oral counts of MS when compared with the xylitol and sorbitol groups.³⁶ Honakala et al³⁷ conducted a randomized clinical trial on school children that compared caries variables in long-term users of erythritol or xylitol candy as compared with a control (sorbitol candy) on dental caries. The children consumed four erythritol, sorbitol, or xylitol candies three to four times a day in school for 3 years. Daily intake of these polyols was about 7.5 g, and caries data were collected at 12 months, 24 months, and 36 months using the International Caries Detection and Assessment System. The fewest number of lesions and the longest time to develop caries were found in the erythritol group.³⁷ In summary, erythritol is thought to be comparable to xylitol in caries prevention; however, more research is needed to support this claim.

MANNITOL

Mannitol (C₆H₁₄O₆) is a sugar alcohol similar to sorbitol. It is found in fruits, leaves, and other parts of plants and mushrooms. For commercial purposes, it is manufactured from fructose, which is derived from cornstarch.

Deshpande and Jadad²⁶ published a systematic review that reported that a combination of sorbitol and mannitol did not affect dental caries with statistical significance. In summary, there is inadequate evidence to support the use of mannitol alone for caries prevention.

MALTITOL

Maltitol (C₁₂H₂₄O₁₁) is a sugar alcohol that is a reduced calorie bulk sweetener manufactured by hydrogenating maltose, which is derived from cornstarch.^24,31 Birkhed et al³⁸ evaluated the effect of maltitol lozenges over 3 months and observed no statistical significant difference in relative numbers of facultative anaerobic bacteria. Edgar and Dodds¹⁸ reported that maltitol affects plaque by in­creasing salivary flow. Holgerson et al³⁹ conducted a randomized clinical trial among school children and reported that xylitol or sorbitol/maltitol reduced the amount of acid production in saliva and dental plaque, but only xylitol interfered with microbial composition. In another randomized clinical trial, Lenkkeri et al⁴⁰ studied caries preventive ef­fects of xylitol/maltitol and erythritol/malti­tol lo­zenges in school children older than 4. These interventions did not provide additional caries-preventive benefits when compared with comprehensive prevention. Thabuis et al⁴¹ conducted a randomized clinical trial on maltitol and xylitol chewing gums in China. The maltitol group showed higher plaque pH and reduction in cariogenic bacteria in the 4-week evaluation. They concluded that sugar-free chewing gums with either maltitol or xylitol could reduce plaque acidogenicity by decreasing the level of oral bacteria present.⁴¹ In summary, there is some evi­dence to support that maltitol affects bacterial acidogenicity but the evidence is lacking on whether it helps prevent caries.

ISOMALT

Isomalt (C₁₂H₂₄O₁₁), a sugar alcohol of hexopyranosyl-hexitol type, is similar to maltitol. It is derived from sucrose with the original glucose-fructose bond remaining intact. The glucose portion is unchanged but the fructose portion is converted into equal amounts of sorbitol and mannitol. As such, isomalt is a mixture of two disaccharide alcohols: gluco-mannitol and gluco-sorbitol.^24,31

Out of the four papers identified that explored isomalt for caries prevention, only one was found to be somewhat relevant, with the effect of isomalt on de- and remineralization of bovine enamel lesions in vitro and in situ.⁴² The authors reported that isomalt facilitated tooth remineralization. In summary, there is inadequate evidence to support the use of isomalt for caries prevention.

HYDROGENATED STARCH HYDROLYSATE

HSH is a bulk sweetener produced by partial hydrolysis of corn, wheat, or potato starch with subsequent hydrogenation of various starch fragments. HSHs include hydrogenated glucose syrups, maltitol syrups, and sorbitol syrups.^24,31

There is little evidence to support the efficacy of HSH in caries prevention. In 1979, Birkhed et al³⁸ evaluated the effect of HSH lozenges over 3 months and observed no statistical significant difference in relative numbers of facultative anaerobes. Thus, there is inadequate evidence to support the use of HSH for caries prevention.

CONCLUSION

The use of sugar alcohols, especially xylitol, remains popular. This has resulted in numerous confections containing xylitol such as candies, lozenges, syrups, chewing gums, toothpastes, and wipes being marketed for caries prevention. It seems prudent that dentists and dental hy­gienists be well-versed with the evidence supporting/refuting the use of such products.

If sugar alcohols are used to replace sugars in between-meal snacks, a reduction in caries may occur. However, there is inconclusive evidence to support the therapeutic effect of commercially available products containing sugar alcohols in various forms and dosages.³⁰

Based on the literature, the following can be observed regarding sugar alcohols:

1. Sugar alcohols do not promote dental caries and are considered passively noncariogenic.
2. The beneficial effects of sugar alcohols may be attributed to the fact that they are nonfermentable and/or promote additional saliva production. However, their abilities as cariostatic agents are not fully established.
3. Currently xylitol is the most promising sugar alcohol for caries prevention but effective doses appear high and remain somewhat unclear. Furthermore, the high dosages used in most studies may be impractical for everyday living.
4. Considering the inadequate evidence of efficacy and possible gastric side effects, it may be premature to support the routine use of any sugar alcohols in caries prevention.

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From Dimensions of Dental Hygiene. May 2016;14(05):58–61.